Role of Chemokines and Their Receptors in the Pathogenesis of HIV Infection

The chemokines comprise a rapidly expanding group of chemotactic cytokines now known to play a critical role in regulating leukocyte trafficking during development and in homeostasis, inflammation, and infection. In the brief period since the original description of platelet factor 4 (PF4) (1) and interferon-inducible protein of 10 kDa (IP-10) (2) this family has grown to more than 50 members. Numerous studies now link chemokines to the pathogenesis of a wide range of inflammatory processes including asthma, atherosclerosis, pneumonia, meningitis, psoriasis, rheumatoid arthritis, inflammatory bowel disease, and sarcoidosis, among others (3). Many also play roles in angiogenesis, hematopoiesis, and fetal development. Chemokine and chemokine receptor genes have also been pirated by pathogens. Many herpes viruses encode chemokine-like molecules as well as functional chemokine receptors. In addition, several intracellular pathogens such as Plasmodium vivax (4), Poxviruses (5) and HIV-1 (6) utilize chemokine receptors to gain access to the cytoplasm of leukocytes. The recent discovery that HIV-1 uses chemokine receptors together with CD4 to enter cells has been a major advance in understanding the pathogenesis of HIV-1 infection and has revealed an entirely new class of therapeutic targets. In this chapter, we briefly review general aspects of chemokine biology (3,7,8), and then examine in detail the role of chemokines and their receptors in the pathogenesis of HIV-1 disease.